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Lactococcus lactis carrying the pValac DNA expression vector coding for IL-10 reduces inflammation in a murine model of experimental colitis.

Zurita-Turk M, Del Carmen S, Santos AC, Pereira VB, Cara DC, Leclercq SY, de LeBlanc Ad, Azevedo V, Chatel JM, LeBlanc JG, Miyoshi A - BMC Biotechnol. (2014)

Bottom Line: Inflammatory bowel diseases (IBD) are intestinal disorders characterized by inflammation in the gastrointestinal tract.Interleukin-10 is one of the most important anti-inflammatory cytokines involved in the intestinal immune system and because of its role in downregulating inflammatory cascades, its potential for IBD therapy is under study.Administration of both L. lactis strains carrying the pValac:il-10 plasmid was effective at diminishing inflammation in this murine model of experimental colitis, showing their potential for therapeutic intervention of IBD.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of General Biology, Institute of Biological Sciences, Federal University of Minas Gerais, Belo Horizonte, Brazil. miyoshi@icb.ufmg.br.

ABSTRACT

Background: Inflammatory bowel diseases (IBD) are intestinal disorders characterized by inflammation in the gastrointestinal tract. Interleukin-10 is one of the most important anti-inflammatory cytokines involved in the intestinal immune system and because of its role in downregulating inflammatory cascades, its potential for IBD therapy is under study. We previously presented the development of an invasive strain of Lactococcus lactis (L. lactis) producing Fibronectin Binding Protein A (FnBPA) which was capable of delivering, directly to host cells, a eukaryotic DNA expression vector coding for IL-10 of Mus musculus (pValac:il-10) and diminish inflammation in a trinitrobenzene sulfonic acid (TNBS)-induced mouse model of intestinal inflammation. As a new therapeutic strategy against IBD, the aim of this work was to evaluate the therapeutic effect of two L. lactis strains (the same invasive strain evaluated previously and the wild-type strain) carrying the therapeutic pValac:il-10 plasmid in the prevention of inflammation in a dextran sodium sulphate (DSS)-induced mouse model.

Results: Results obtained showed that not only delivery of the pValac:il-10 plasmid by the invasive strain L. lactis MG1363 FnBPA+, but also by the wild-type strain L. lactis MG1363, was effective at diminishing intestinal inflammation (lower inflammation scores and higher IL-10 levels in the intestinal tissues, accompanied by decrease of IL-6) in the DSS-induced IBD mouse model.

Conclusions: Administration of both L. lactis strains carrying the pValac:il-10 plasmid was effective at diminishing inflammation in this murine model of experimental colitis, showing their potential for therapeutic intervention of IBD.

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Influence of DSS and different bacterial administrations on gut secretory IgA. Intestinal fluid was collected and total sIgA was measured by ELISA of wild-type mice, DSS wild-type mice and diseased mice that received the L. lactis MG1363 strain, L. lactis MG1363 pValac:il-10 strain, L. lactis MG1363 FnBPA + strain or L. lactis MG1363 FnBPA + pValac:il-10 strain during treatment. Bars represent the mean N = 6 ± SD of two independent experiments. Asterisks represent statistical significance *p < 0.05 or **p < 0.001).
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Figure 3: Influence of DSS and different bacterial administrations on gut secretory IgA. Intestinal fluid was collected and total sIgA was measured by ELISA of wild-type mice, DSS wild-type mice and diseased mice that received the L. lactis MG1363 strain, L. lactis MG1363 pValac:il-10 strain, L. lactis MG1363 FnBPA + strain or L. lactis MG1363 FnBPA + pValac:il-10 strain during treatment. Bars represent the mean N = 6 ± SD of two independent experiments. Asterisks represent statistical significance *p < 0.05 or **p < 0.001).

Mentions: Secretory IgA creates a first-line of defence against mucosal compromise that is lost during IBD. Therefore, sIgA levels from intestinal fluids of mice were also analysed. It was observed that only mice that received the L. lactis MG1363 FnBPA + pValac:il-10 strain showed a significant increase in the concentration of sIgA when compared to those from the control group, DSS group and the groups that did not receive the strains carrying the pValac:il-10 plasmid (Figure 3). Moreover, this strain also induced an increased sIgA production when compared to the non-invasive L. lactis MG1363 pValac:il-10 strain.


Lactococcus lactis carrying the pValac DNA expression vector coding for IL-10 reduces inflammation in a murine model of experimental colitis.

Zurita-Turk M, Del Carmen S, Santos AC, Pereira VB, Cara DC, Leclercq SY, de LeBlanc Ad, Azevedo V, Chatel JM, LeBlanc JG, Miyoshi A - BMC Biotechnol. (2014)

Influence of DSS and different bacterial administrations on gut secretory IgA. Intestinal fluid was collected and total sIgA was measured by ELISA of wild-type mice, DSS wild-type mice and diseased mice that received the L. lactis MG1363 strain, L. lactis MG1363 pValac:il-10 strain, L. lactis MG1363 FnBPA + strain or L. lactis MG1363 FnBPA + pValac:il-10 strain during treatment. Bars represent the mean N = 6 ± SD of two independent experiments. Asterisks represent statistical significance *p < 0.05 or **p < 0.001).
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4129430&req=5

Figure 3: Influence of DSS and different bacterial administrations on gut secretory IgA. Intestinal fluid was collected and total sIgA was measured by ELISA of wild-type mice, DSS wild-type mice and diseased mice that received the L. lactis MG1363 strain, L. lactis MG1363 pValac:il-10 strain, L. lactis MG1363 FnBPA + strain or L. lactis MG1363 FnBPA + pValac:il-10 strain during treatment. Bars represent the mean N = 6 ± SD of two independent experiments. Asterisks represent statistical significance *p < 0.05 or **p < 0.001).
Mentions: Secretory IgA creates a first-line of defence against mucosal compromise that is lost during IBD. Therefore, sIgA levels from intestinal fluids of mice were also analysed. It was observed that only mice that received the L. lactis MG1363 FnBPA + pValac:il-10 strain showed a significant increase in the concentration of sIgA when compared to those from the control group, DSS group and the groups that did not receive the strains carrying the pValac:il-10 plasmid (Figure 3). Moreover, this strain also induced an increased sIgA production when compared to the non-invasive L. lactis MG1363 pValac:il-10 strain.

Bottom Line: Inflammatory bowel diseases (IBD) are intestinal disorders characterized by inflammation in the gastrointestinal tract.Interleukin-10 is one of the most important anti-inflammatory cytokines involved in the intestinal immune system and because of its role in downregulating inflammatory cascades, its potential for IBD therapy is under study.Administration of both L. lactis strains carrying the pValac:il-10 plasmid was effective at diminishing inflammation in this murine model of experimental colitis, showing their potential for therapeutic intervention of IBD.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of General Biology, Institute of Biological Sciences, Federal University of Minas Gerais, Belo Horizonte, Brazil. miyoshi@icb.ufmg.br.

ABSTRACT

Background: Inflammatory bowel diseases (IBD) are intestinal disorders characterized by inflammation in the gastrointestinal tract. Interleukin-10 is one of the most important anti-inflammatory cytokines involved in the intestinal immune system and because of its role in downregulating inflammatory cascades, its potential for IBD therapy is under study. We previously presented the development of an invasive strain of Lactococcus lactis (L. lactis) producing Fibronectin Binding Protein A (FnBPA) which was capable of delivering, directly to host cells, a eukaryotic DNA expression vector coding for IL-10 of Mus musculus (pValac:il-10) and diminish inflammation in a trinitrobenzene sulfonic acid (TNBS)-induced mouse model of intestinal inflammation. As a new therapeutic strategy against IBD, the aim of this work was to evaluate the therapeutic effect of two L. lactis strains (the same invasive strain evaluated previously and the wild-type strain) carrying the therapeutic pValac:il-10 plasmid in the prevention of inflammation in a dextran sodium sulphate (DSS)-induced mouse model.

Results: Results obtained showed that not only delivery of the pValac:il-10 plasmid by the invasive strain L. lactis MG1363 FnBPA+, but also by the wild-type strain L. lactis MG1363, was effective at diminishing intestinal inflammation (lower inflammation scores and higher IL-10 levels in the intestinal tissues, accompanied by decrease of IL-6) in the DSS-induced IBD mouse model.

Conclusions: Administration of both L. lactis strains carrying the pValac:il-10 plasmid was effective at diminishing inflammation in this murine model of experimental colitis, showing their potential for therapeutic intervention of IBD.

Show MeSH
Related in: MedlinePlus